Enzyme kinetics far from the standard quasi-steady-state and equilibrium approximations

Analytic approximations of the time-evolution of the single enzyme-substrate reaction are valid for all but a small region of parameter space in the positive initial enzyme-initial substrate concentration plane. We find velocity equations for the substrate decomposition and product formation with the aid of the total quasi-steady-state approximation and an aggregation technique for cases where neither the more normally employed standard nor reverse quasi-steady-state approximations are valid. Applications to determining reaction kinetic parameters are discussed

A century of enzyme kinetics. Should we believe in the Km and vmax estimates?

The application of the quasi-steady-state approximation (QSSA) in biochemical kinetics allows the reduction of a complex biochemical system with an initial fast transient into a simpler system. The simplified system yields insights into the behavior of the biochemical reaction, and analytical approximations can be obtained to determine its kinetic parameters. However, this process can lead to inaccuracies due to the inappropriate application of the QSSA. Here we present a number of approximate solutions and determine in which regions of the initial enzyme and substrate concentration parameter space they are valid. In particular, this illustrates that experimentalists must be careful to use the correct approximation appropriate to the initial conditions within the parameter space

Multiscale modeling in biology

The 1966 science-fction film Fantastic Voyage captured the public imagination with a clever idea: what fantastic things might we see and do if we could minaturize ourselves and travel through the bloodstream as corpuscles do? (This being Hollywood, the answer was that we'd save a fellow scientist from evildoers.

A mathematical investigation of a clock and wavefront model for somitogenesis

Abstract Somites are transient blocks of cells that form sequentially along the antero-posterior axis of vertebrate embryos. They give rise to the vertebrae, ribs and other associated features of the trunk. In this work we develop and analyse a mathematical formulation of a version of the Clock and Wavefront model for somite formation, where the clock controls when the boundaries of the somites form and the wavefront determines where they form. Our analysis indicates that this interaction between a segmentation clock and a wavefront can explain the periodic pattern of somites observed in normal embryos. We can also show that a simplification of the model provides a mechanism for predicting the anomalies resulting from perturbation of the wavefront

Formation of vertebral precursors: Past models and future predictions

Disruption of normal vertebral development results from abnormal formation and segmentation of the vertebral precursors, called somites. Somitogenesis, the sequential formation of a periodic pattern along the antero-posterior axis of vertebrate embryos, is one of the most obvious examples of the segmental patterning processes that take place during embryogenesis and also one of the major unresolved events in developmental biology. We review the most popular models of somite formation: Cooke and Zeeman's clock and wavefront model, Meinhardt's reaction-diffusion model and the cell cycle model of Stern and co-workers, and discuss the consistency of each in the light of recent experimental findings concerning FGF-8 signalling in the presomitic mesoderm (PSM). We present an extension of the cell cycle model to take account of this new experimental evidence, which shows the existence of a determination front whose position in the PSM is controlled by FGF-8 signalling, and which controls the ability of cells to become competent to segment. We conclude that it is, at this stage, perhaps erroneous to favour one of these models over the others

Formation of vertebral precursors: Past models and future predictions

Disruption of normal vertebral development results from abnormal formation and segmentation of the vertebral precursors, called somites. Somitogenesis, the sequential formation of a periodic pattern along the antero-posterior axis of vertebrate embryos, is one of the most obvious examples of the segmental patterning processes that take place during embryogenesis and also one of the major unresolved events in developmental biology. We review the most popular models of somite formation: Cooke and Zeeman's clock and wavefront model, Meinhardt's reaction-diffusion model and the cell cycle model of Stern and co-workers, and discuss the consistency of each in the light of recent experimental findings concerning FGF-8 signalling in the presomitic mesoderm (PSM). We present an extension of the cell cycle model to take account of this new experimental evidence, which shows the existence of a determination front whose position in the PSM is controlled by FGF-8 signalling, and which controls the ability of cells to become competent to segment. We conclude that it is, at this stage, perhaps erroneous to favour one of these models over the others

Waves and patterning in developmental biology: vertebrate segmentation and feather bud formation as case studies

In this article we will discuss the integration of developmental patterning mechanisms with waves of competency that control the ability of a homogeneous field of cells to react to pattern forming cues and generate spatially heterogeneous patterns. We base our discussion around two well known patterning events that take place in the early embryo: somitogenesis and feather bud formation. We outline mathematical models to describe each patterning mechanism, present the results of numerical simulations and discuss the validity of each model in relation to our example patterning processes

A mathematical basis for the clock and wavefront model for somitogenesis

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A mathematical formulation for the cell-cycle model in somitogenesis: analysis, parameter constraints and numerical solutions

In this work we present an analysis, supported by numerical simulations, of the formulation of the cell-cycle model for somitogenesis proposed in Collier et al.(J. Theor. Biol. 207 (2000), 305–316). The analysis indicates that by introducing appropriate parameter constraints on model parameters the cell-cycle mechanism can indeed give rise to the periodic pattern of somites observed in normal embryos. The analysis also provides a greater understanding of the signalling process controlling somite formation and allows us to understand which parameters influence somite length